UNIPROT:P10415 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UNIPROT:P10415 (Bcl-2)
33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemia-reperfusion injury (IRI) contributes to early and late dysfunction of liver transplants. We have shown that sentinel Toll-like receptor-4 (TLR4) plays a key role in the activation of T cell immune responses during hepatic IRI. We have also documented that overexpression of heme oxygenase-1 (HO-1) exerts potent cytoprotective effects. This study analyzes how adenovirus (Ad)-based viral interleukin-10 (vIL-10) gene transfer affects TLR4 and HO-1 signaling in host innate and adaptive immunity during liver IRI. Using a partial lobar warm IRI model, groups of wild-type and HO-1(+/-) knockout (KO) mice were assessed for severity of hepatocellular damage after 90 min of warm ischemia followed by 6 hr of reperfusion. Both wild-type and HO-1 (+/-) KO mice treated with Ad-vIL-10 have shown improved hepatic function (serum glutamic-oxaloacetic transaminase levels), ameliorated histological signs of IRI (Suzuki's score), decreased neutrophil accumulation (myeloperoxidase activity), and depressed tumor necrosis factor-alpha/IL-1beta, IL-2/interferon-gamma, E-selectin, and macrophage inflammatory protein-2 expression. These effects were IL-10 dependent as treatment with neutralizing antibody re-created liver IRI. In contrast, untreated wild-type and HO-1 (+/-) KO mice, as well as wild-type and HO-1 (+/-) KO mice treated with Ad-beta-Gal, showed severe hepatocellular damage due to IRI. Unlike in controls, wild-type and HO-1 (+/-) KO mice treated with Ad-vIL-10 revealed markedly depressed TLR4 and NF-kappaB expression, along with increased HO-1 and Bcl-2/Bcl-x(L) expression, as compared with respective controls. Thus, vIL-10 gene transfer prevents hepatic IRI in association with depressed expression of innate TLR4, and adaptive Th1 cytokine/chemokine programs. The induction of antioxidant HO-1 and anti-apoptotic Bcl-2/Bcl-x(L) by vIL-10 exerts synergistic cytoprotective function against antigen-independent hepatic inflammatory response triggered by IRI.
...
PMID:Viral interleukin-10 gene transfer prevents liver ischemia-reperfusion injury: Toll-like receptor-4 and heme oxygenase-1 signaling in innate and adaptive immunity. 1743 57

Alzheimer's disease (AD) is the most common form of dementia. Glucagon-like peptide-1 (GLP-1) gives a new genre in therapeutic targets for intervention in AD with its neurotrophic and neuroprotective functions. In previous work, we identified that geniposide is a novel agonist for GLP-1 receptor, which shows neurotrophic characteristics to induce the neuronal differentiation of PC12 cells. The aim of this study is to determine whether geniposide prevents neurons from oxidative damage, and to explore its signaling pathways. The results demonstrated that geniposide increased the expression of anti-apoptotic proteins, including Bcl-2 and heme oxygenase-1 (HO-1), to antagonize the oxidative damage in PC12 cells induced by hydrogen peroxide. LY294002 (a PI3K inhibitor) inhibited the effect of geniposide increasing of Bcl-2 level by activation of MAPK, MEK and c-Raf phosphorylation in hydrogen peroxide treated PC12 cells. U0126 (a selective inhibitor of MEK) also attenuated the enhancement of geniposide on Bcl-2 level by inhibiting the phosphorylation of p90RSK in the hydrogen peroxide treated PC12 cells. All these data demonstrate that geniposide, an agonist for GLP-1 receptor, regulates expression of anti-oxidative proteins including HO-1 and Bcl-2 by activating the transcriptor of p90RSK via MAPK signaling pathway in PC12 cells.
...
PMID:Geniposide, a novel agonist for GLP-1 receptor, prevents PC12 cells from oxidative damage via MAP kinase pathway. 1762 57

The optimal kidney preservation system and methods to ameliorate reperfusion injury are major factors in accomplishing successful graft function following transplantation. Ischaemia and reperfusion lead to cellular stress and the adaptive response may include the activation of genes involved in cellular protection and/or cell death by apoptosis. We investigated the expression of cytoprotective heme oxygenase-1 (HO-1), anti-apoptotic Bcl-2 and pro-apoptotic Bax after 6 h isolated organ perfusion in porcine kidneys that had been given 10 and 40 min warm ischaemic time. The level of HO-1 was shown to be significantly higher in the 10-min warm ischaemic group compared with 40-min group (0.90 +/- 0.03 vs. 0.83 +/- 0.03; P = 0.002). The levels of HO-1 showed a significant positive correlated with parameters of renal function, creatinine clearance, and renal blood flow and urine output (AUC; r = 0.8042, P = 0.03; r = 0.6028, P = 0.04; r = 0.6055, P = 0.04), demonstrating a possible protective role of this gene in this model of renal transplantation.
...
PMID:Differential expression of cytoprotective and apoptotic genes in an ischaemia-reperfusion isolated organ perfusion model of the transplanted kidney. 1763 10

In the present study, the protective effect of melatonin on sodium arsenite (arsenite)-induced apoptosis was investigated. Local infusion of arsenite elevated lipid peroxidation and depleted glutathione content in the infused substantia nigra (SN), as well as reduced striatal dopamine content. Systemic administration of melatonin diminished arsenite-induced oxidative injury. Furthermore, melatonin attenuated arsenite-induced increases in heat shock protein 70 and heme oxygenase-1 as well as phosphorylation of p38 mitogen-activated protein kinase and elevations in cyclooxygenase II and inducible nitric oxide synthase expression. Inhibition by melatonin of arsenite-induced apoptosis was determined by its attenuation of DNA fragmentation and terminal deoxytransferase-mediated dUTP-nick end labeling's positive cells in the infused SN of melatonin-treated rats. Melatonin reduced arsenite-induced apoptosis through mitochondrial and endoplasmic reticulum (ER) pathways. In the mitochondrial pathway, systemic melatonin inhibited arsenite-induced elevations in Bcl-2 and cytosolic cytochrome c as well as arsenite-induced reductions in procaspase-3 levels and elevations in active caspase-3 levels in the infused SN. Regarding the ER pathway, melatonin attenuated arsenite-induced elevations in activating transcription factor-4, CCAAT/enhancer binding protein (C/EBP) homologues protein, X-bon binding protein (XBP-1) and cytosolic immunoglobulin binding protein (BIP) as well as reductions in procaspase 12 levels. Moreover, aggregation of alpha-synuclein was reduced in the arsenite-infused SN of melatonin-treated rats. Our in vitro data showed that melatonin ameliorated arsenite-induced lipid peroxidation. Taken together, our data suggest that melatonin is neuroprotective against arsenite-induced oxidative injury in the nigrostriatal dopaminergic system of rat brain. Furthermore, the neuroprotective effects by melatonin on arsenite-induced apoptosis were mediated via inhibiting both mitochondrial and ER pathways. Accordingly, melatonin may be therapeutically useful for the treatment of arsenite-induced apoptosis in central nervous system.
...
PMID:Melatonin attenuates arsenite-induced apoptosis in rat brain: involvement of mitochondrial and endoplasmic reticulum pathways and aggregation of alpha-synuclein. 1764 94

Radiocontrast agents are thought to induce acute kidney injury in part through increased production of reactive oxygen species and increased cellular apoptosis. In this study we determined whether heme oxygenase-1 could prevent or reduce radiocontrast-induced acute kidney injury and, if so, what were the mechanisms by which this can occur. Sodium iothalamate was administered to uninephrectomized, salt-depleted male Sabra rats to initiate acute kidney injury. Heme oxygenase-1 was induced with cobalt protoporphyrin or inhibited with stannous mesoporphyrin. Inhibition of heme oxygenase exacerbated kidney injury as measured by an increase in plasma creatinine and in superoxide production. Heme oxygenase-1 induction prevented the increase in plasma creatinine and in superoxide in both the cortex and medulla compared to untreated rats with acute kidney injury. This protective effect of heme oxygenase-1 was associated with increased anti-apoptotic proteins Bcl-2 and Bcl-xl and a decrease of pro-apoptotic caspase-3 and caspase-9 along with increased expression of inactive BAX. Our study suggests that increased levels of heme oxygenase-1 are protective against acute kidney injury due to radiocontrast exposure.
...
PMID:Heme oxygenase-1 protects against radiocontrast-induced acute kidney injury by regulating anti-apoptotic proteins. 1791 15

In the central nervous system oxidative stress has been implicated in the pathology of several neurological disorders. The ability to withstand reactive oxygen species and oxidative stress are essential for survival and therefore all aerobic cells are endowed with chemical and enzymatic antioxidative defense systems. The purpose of the present study was to investigate the antioxidative response at the transcriptional level following exposure of primary astrocytes to a pro-oxidant, Paraquat (PQ). This was done by investigating the time-dependent expression of selected genes encoding the antioxidative enzymes Mn- and CuZn superoxide dismutase (SOD) and catalase as well as the transcription factor component AP-1. Paraquat induced the expression of Mn- and CuZn SOD, catalase and decreases the expression of c-jun (a part of AP-1). Furthermore, the gene expression profiles were investigated after exposure to PQ using a commercial cDNA membrane array containing 207 genes from key oxidative stress pathways. The gene expression pattern clearly indicated that 60 microM PQ for 48 h induces genes related to oxidative stress, detoxification, mitotic arrest, DNA repair, and apoptosis. The PQ (48 h)-induced expressions of genes identified in cDNA array were confirmed by Northern blot analysis, which revealed a statistical significant up-regulation of genes involved in oxidative stress, detoxification, and DNA repair/synthesis and includes heme oxygenase-1 (11-fold), NAD(P)H dehydrogenase (8-fold), glutathione S-transferase P (7-fold), glucose-regulated 78-kDa protein (7-fold), glucose-regulated 75-kDa protein (6-fold), and growth-arrest and DNA-damage-inducible protein 45 (4.5-fold) and minor changes for heat shock 10-kDa protein, NADPH-cytochrome P450 reductase, heme oxygenase-2, proliferating cell nuclear antigen, and Bcl-2-associated death promoter. Thus, we could demonstrate a PQ-inducible effect of the mRNA of antioxidative enzymes, as well as the mRNAs of possible enzymes involved in the protection against oxidative stress.
...
PMID:Characterization of the transcriptional profile in primary astrocytes after oxidative stress induced by Paraquat. 1793 86

Ischaemic pre-conditioning has a powerful protective potential against ischaemia-induced cell death, and acidosis is an important feature of ischaemia and can lead to apoptosis. Here we tested whether pre-conditioning with acidosis, that is, acidic pre-conditioning (APC), may protect coronary endothelial cells (EC) against apoptosis induced by simulated ischaemia. For pre-conditioning, EC were exposed fo 40 min. to acidosis (pH 6.4) followed by a 14-hrs recovery period (pH 7.4) and finally treated for 2 hrs with simulated ischaemia (glucose-free anoxia at pH 6.4). Cells undergoing apoptosis were visualized by chromatin staining or by determination of caspase-3 activity Simulated ischaemia in untreated EC increased caspase-3 activity and the number of apoptotic cell (31.3 +/- 1.3%versus 3.9 +/- 0.6% in control). APC significantly reduced the rate of apoptosis (14.2 +/- 1.3%) and caspase-3 activity. Western blot analysis exploring the under lying mechanism leading to this protection revealed suppression of the endoplasmic reticulum- (reduced cleavage of caspase-12) and mitochondria-mediated (reduced cytochrome C release) pathways of apoptosis. These effects were associated with an over-expression of the anti-apoptotic protein Bcl-xL 14 hrs after APC, whereas no effect on the expression of Bcl-2, Bax, Bak, procaspase-12, reticulum-localized chaperones (GRP78, calreticulin), HSP70, HSP32 and HSP27 could be detected. Knock-down of Bcl-xL by siRNA-treatment prevented the protective effect of APC. In conclusion, short acidic pre-treatment can protect EC against ischaemic apoptosis. The mechanism of this protection consists of suppression of the endoplasmic reticulum- and mitochondria-mediated pathways. Over-expression of the anti apoptotic protein Bcl-xL is responsible for the increased resistance to apoptosis during ischaemic insult.
...
PMID:Acidic pre-conditioning suppresses apoptosis and increases expression of Bcl-xL in coronary endothelial cells under simulated ischaemia. 1805 90

Chronic exposure to arsenic causes health problems, including peripheral neuropathy. Oxidative stress is one of the mechanisms underlying arsenic-induced neurotoxicity. For this report, we studied the protective effect of N-acetylcysteine (NAC) on arsenic-induced oxidative injury in dorsal root ganglion (DRG) explants. After 24-h incubation, NAC concentration-dependently attenuated arsenite-induced depletion in glutathione (GSH) content and increases in the ratio of oxidized GSH/reduced GSH (GSSG/GSH ratio) in DRG explants. Furthermore, NAC inhibited arsenite-induced elevation in the expression of stress proteins, such as heat shock protein 70 and heme oxygenase 1, as well as arsenite-induced phosphorylation of p38 mitogen-activated protein kinase. Incubation with NAC ameliorated arsenite-induced apoptosis by abolishing both mitochondrial and endoplasmic reticulum (ER) pathways. In the mitochondrial pathway, NAC attenuated arsenite-induced elevation in Bcl-2 level and cytosolic cytochrome c, as well as arsenite-induced reduction in procaspase-3 levels. In the ER pathway, NAC suppressed arsenite-induced increases in activating transcription factor 6 and C/EBP homologous protein in the nuclear fraction. Furthermore, arsenite-induced reductions in procaspase-12 and elevation in BIP and caspase-12, an ER-specific enzyme, were prevented after NAC incubation. Taken together, our results demonstrate that NAC is neuroprotective against arsenite-induced oxidative injury in DRG explants. Furthermore, NAC inhibits arsenite-induced toxicity by inhibiting ER and mitochondrion activation. Our data indicate that NAC is potentially therapeutic for arsenite-induced peripheral neuropathy.
...
PMID:N-acetylcysteine attenuates arsenite-induced oxidative injury in dorsal root ganglion explants. 1807 80

Doxorubicin, a widely used chemotherapeutic agent, can give rise to severe cardiotoxicity by inducing cardiomyocyte apoptosis. Dracocephalum rupestre Hance, a Chinese traditional herb, has therapeutic potential for cardiovascular diseases. Naringenin-7-O-glucoside is the main active constituent of D. rupestre and there is increasing interest in its therapeutic applications. The aim of this study was to evaluate the effects of naringenin-7-O-glucoside on cardiomyocyte apoptosis induced by doxorubicin. Cell viability was detected by MTT assay. Naringenin-7-O-glucoside (10, 20, and 40 microM) significantly enhanced cardiomyocyte proliferation relative to that of doxorubicin. Furthermore, naringenin-7-O-glucoside increased the protein levels of heme oxygenase-1 (HO-1) and Bcl-2 in cardiomyocytes (as detected by Western blotting) and suppressed the mRNA expression of caspase-3 and caspase-9 (as detected by RT-PCR). These results suggest that naringenin-7-O-glucoside has protective effects against doxorubicin-induced apoptosis, effects which could underlie the use of naringenin-7-O-glucoside therapeutic agent for treating or preventing cardiomyopathy associated with doxorubicin.
...
PMID:Protective effects of naringenin-7-O-glucoside on doxorubicin-induced apoptosis in H9C2 cells. 1815 51

Hemorrhagic shock (HS) is an oxidative stress that causes intestinal tissue injury. Heme oxygenase 1 (HO-1) is induced by oxidative stress and is thought to play an important role in the protection of tissues from oxidative injury. We previously reported the ileum to be the most susceptible to HS-induced tissue injury site in the intestine because HO-1 induction is the lowest at this site. We also previously demonstrated that glutamine (GLN) significantly induced HO-1 in the lower intestinal tract. In the present study, we investigated whether GLN pretreatment improves HS-induced intestinal tissue injury in the ileum by HO-1 induction. Treatment of rats with GLN (0.75 g/kg, i.v.) markedly induced functional HO-1 protein in mucosal epithelial cells in the ileum. Glutamine treatment before HS (MAP of 30 mmHg for 60 min) significantly ameliorated HS-induced mucosal inflammation and apoptotic cell death in the ileum, as judged by significant decreases in gene expression of TNF-alpha, iNOS, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1, myeloperoxidase activity, the number of infiltrated neutrophils, DNA fragmentation by in situ oligo ligation assay, and activated caspase-3 expression, and by increases in gene expression of IL-10 and Bcl-2. In contrast, treatment with tin mesoporphyrin, a specific inhibitor of HO activity, abolished the beneficial effect of GLN pretreatment. These findings indicate that GLN pretreatment significantly ameliorated tissue injury in the ileum after HS by inducing HO-1. Glutamine treatment may thus protect mucosal cells from HS-induced oxidative damage via the anti-inflammatory and antiapoptotic properties of HO-1.
...
PMID:Prevention of hemorrhagic shock-induced intestinal tissue injury by glutamine via heme oxygenase-1 induction. 1849 9

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>